Holmium phosphate nanoparticles as negative contrast agents for high-field magnetic resonance imaging: Synthesis, magnetic relaxivity study and in vivo evaluation.

The increasing use of high magnetic fields in magnetic resonance imaging (MRI) scanners demands new contrast agents, since those used in low field instruments are not effective at high fields. In this paper, we report the synthesis of a negative MRI contrast agent consisting of HoPO nanoparticles (NPs). Three different sizes (27 nm, 48 nm and 80 nm) of cube-shaped NPs were obtained by homogeneous precipitation in polyol medium and then coated with poly(acrylic) acid (PAA) to obtain stable colloidal suspensions of HoPO@PAA NPs in physiological medium (PBS). The transverse relaxivity (r) of aqueous suspensions of the resulting NPs was evaluated at both 1.44 T and 9.4 T. A positive correlation between r values and field strength as well as between r values and particle size at both magnetic field strengths was found although this correlation failed for the biggest NPs at 9.4 T, likely due to certain particles aggregation inside the magnet. The highest r value (489.91 mMs) was found for the 48 nm NPs at 9.4 T. Toxicity studies demonstrated that the latter NPs exhibited low toxicity to living systems. Finally, in vivo studies demonstrated that HoPO@PAA NPs could be a great platform for next-generation T-weighted MRI contrast agents at high magnetic field.